Reducing ventral hippocampal CA1/subiculum hyperexcitability restores social memory and alleviates anxiety-related behavior in a mouse model of temporal lobe epilepsy.

ABSTRACT:

Background

Interictal cognitive and affective comorbidities in temporal lobe epilepsy (TLE) often remain refractory to seizure-directed therapies. We tested the causal role of ventral hippocampal CA1/subiculum (vCA1/Sub) hyperexcitability in social memory failure and anxiety-related behavior, and whether normalizing principal-cell excitability restores function.

Methods

In pilocarpine-treated mice we combined blinded behavioral assays (social approach/discrimination, open field, olfaction), whole-cell recordings from mCherry-labeled vCA1/Sub principal neurons, alveus stimulation to assay synaptic inhibition/excitation, immunohistochemistry for parvalbumin (PV) and somatostatin (SST) interneurons, and chemogenetic control of excitability (hM3Dq in controls; hM4Di and KORD in

SUBMITTER: Goodman A 

PROVIDER: S-EPMC12458119 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature